Is resurgent Na+ current an alpha-subunit-specific property? Maybe not. Focus on "Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice".

Abstract

+During the past quarter century Na channels have slowly but steadily revealed their kinetic complexity and diversity. Far beyond the one-trick pony of the Hodgkin-Huxley Na channel that rapidly activates and inactivates to produce action potentials, Na channels continue to display an ever-increasing variety of kinetic properties such as persistence, slow-inactivation, and most recently “resurgence.” Resurgent current flows when an open-channel block is relieved by rapid repolarization from positive potentials. Resurgent current immediately after an action potential may promote firing of a subsequent spike not only because of the inward current itself, but also because the flow of this current is associated with a more rapid recovery from inactivation (Raman and Bean 2001). Resurgent currents were first described in Purkinje cells where they improve high-frequency firing (Raman and Bean 1997). More recently, resurgent currents have also been implicated in rhythmic firing of neurons in the subthalamic nucleus, an area gaining importance in the treatment of end-stage Parkinson’s syndromes (Do and Bean 2003). Few neurons throughout the brain, however, are known to display resurgent currents, suggesting that these currents are carried by a select subset of Na channels. Compelling evidence that this subset corresponds to one particular Na channel subunit is the finding that Purkinje cells lacking Nav1.6 alpha subunits (med mutant) do not display resurgent currents. However, under conditions of artificially induced slowing of inactivation by beta-pompilidotoxin, the remaining Na channels could be made to produce a resurgent current (Grieco and Raman 2004). The report by Do and Bean (this issue, p. 726 –733) sheds further light on this story. By identifying resurgent current in subthalamic nucleus neurons from mice lacking the Nav1.6 alpha subunits, they demonstrate that resurgent current is not a property unique to Nav1.6 subunits. Do and Bean’s findings suggest instead that some form of modulation or an association with an auxiliary subunit, rather than the specific alpha subunit, is critical for the production of resurgent current. Such an association would need to produce a secondary inactivation to compete with classical fast inactivation. Whatever the nature of this putative element, different classes of neurons may rely on different Na channel alpha-subunits to produce resurgent currents. Resurgent currents may indeed represent a more ubiquitous determinant of cell-specific firing than we now appreciate.